GLP-1 Receptor Agonist Dosing
Start semaglutide at 0.25 mg subcutaneously once weekly for 4 weeks, then increase to 0.5 mg weekly, with further escalation to 1.0 mg and potentially 2.0 mg at 4-week intervals if glycemic targets are not met. 1
Semaglutide (Ozempic) Dosing Protocol
Initial Titration Schedule
- Begin with 0.25 mg subcutaneously once weekly for exactly 4 weeks to minimize gastrointestinal side effects, particularly nausea which occurs in 18% of patients 1
- After 4 weeks, increase to 0.5 mg once weekly, which serves as the standard maintenance dose for most patients 1
- If HbA1c targets remain unmet after at least 4 weeks on 0.5 mg, escalate to 1.0 mg once weekly 1, 2
- For patients requiring maximum glycemic control and weight loss, increase to 2.0 mg once weekly after at least 4 weeks on 1.0 mg 1
Administration Details
- Inject subcutaneously in the abdomen, thigh, or upper arm at any time of day, with or without meals 1, 2
- The weekly injection day can remain consistent but timing during that day is flexible 1
Liraglutide (Victoza) Dosing Protocol
Initial Titration Schedule
- Start at 0.6 mg subcutaneously once daily for at least 1 week to improve gastrointestinal tolerability 3, 4
- After 1 week, increase to 1.2 mg once daily, which is the standard maintenance dose 3, 4
- For patients requiring additional glycemic control, increase to the maximum dose of 1.8 mg once daily after at least 1 week on 1.2 mg 3, 4
Administration Details
- Administer once daily at any time of day, independent of meals 4
- Inject subcutaneously in the abdomen, thigh, or upper arm 3
Dosing in Renal Impairment
No Dose Adjustment Required
- GLP-1 receptor agonists including liraglutide, semaglutide, and dulaglutide require no dose adjustment for any degree of renal impairment, including end-stage renal disease 5, 1
- These agents have been studied in patients with eGFR as low as 15 mL/min/1.73 m² 5
- The MACE risk reduction with liraglutide was significantly greater in patients with eGFR <60 mL/min/1.73 m² compared to those with eGFR ≥60 mL/min/1.73 m² 5
Special Considerations in Advanced CKD
- GLP-1 receptor agonists can be safely used in moderate-to-severe CKD (stages G3 and G4) 5
- Gastrointestinal side effects occur in 15-20% of patients with CKD stages G3-G4 but are usually tolerable with dose titration and resolve over several weeks to months 5
Dosing in Hepatic Impairment
- No dose adjustments are required for hepatic impairment of any severity 1
Critical Dosing Pitfalls to Avoid
Do Not Skip the Starting Dose
- Never skip the initial low-dose titration period (0.25 mg for semaglutide, 0.6 mg for liraglutide), as this is essential to minimize gastrointestinal side effects that cause treatment discontinuation in 8-10% of patients 1
Do Not Escalate Too Rapidly
- Allow at least 4 weeks at each semaglutide dose level before increasing 1, 2
- Allow at least 1 week at each liraglutide dose level before increasing 3, 4
- Rapid escalation increases the risk of nausea, vomiting, and diarrhea leading to discontinuation 5
Concomitant Medication Adjustments
- When adding GLP-1 receptor agonists to existing insulin therapy, reduce basal insulin dose by 20% to prevent hypoglycemia 6, 3
- When used with sulfonylureas, consider reducing the sulfonylurea dose to minimize hypoglycemia risk 4, 7
- Monitor patients taking medications with narrow therapeutic index (e.g., warfarin) due to delayed gastric emptying effects 1
Absolute Contraindications
- Personal or family history of medullary thyroid carcinoma 1, 6
- Multiple endocrine neoplasia syndrome type 2 (MEN2) 1, 6
- Pregnancy or lactation 1, 6
- History of severe hypersensitivity reaction to the specific GLP-1 receptor agonist 1, 3
Agent Selection Based on Outcomes
For Cardiovascular Risk Reduction
- Prioritize semaglutide, liraglutide, or dulaglutide, as these have demonstrated cardiovascular benefit in large outcome trials 5
- These agents reduced major adverse cardiovascular events (MACE) by 20-26% in patients with established atherosclerotic cardiovascular disease 6, 8